Effect of JTV-506, a novel vasodilator, on experimental angina model in rats.
The antianginal effects of JTV-506, a newly synthesized 2,2-bis-methoxymethyl benzopyran-derivative potassium channel opener, were evaluated in experimental angina models in rats and compared with those of levcromakalim, nicorandil, and nifedipine. JTV-506 (0.01-0.1 mg/kg, i.d.) dose-dependently inhibited S-wave elevation induced by injection of methacholine but caused almost no changes in blood pressure or heart rate. Other vasodilators including levcromakalim, nicorandil, and nifedipine, when administered intraduodenally, also inhibited the S-wave elevation and elicited a decrease in blood pressure. Oral administration of JTV-506 (1 and 3 mg/kg), levcromakalim (1 and 3 mg/kg), and nicorandil (30 mg/kg) significantly inhibited the S-wave depression induced by intravenous administration of arginine vasopressin (AVP). Thus JTV-506 exerts a potent protective effect on angina pectoris models to an extent similar to those of levcromakalim, nicorandil, and nifedipine, whereas its action on systemic blood pressure is different from that of other vasodilators, including reference potassium channel openers. These results suggest that JTV-506 may clinically be useful as an antianginal agent.
Hirata
Y
Y
Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco, Inc., Takatsuki, Osaka.
Miyai
H
H
Mabuchi
Y
Y
Aisaka
K
K
D000284:Administration, Oral; D000787:Angina Pectoris / Q000188:drug therapy*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002839:Chromans / Q000627:therapeutic use*; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D015394:Molecular Structure; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000627:therapeutic use*
D002839:Chromans; C107494:JTV 506; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D016210:Methacholine Chloride; D001127:Arginine Vasopressin; D009536:Niacinamide; D020108:Nicorandil; D009543:Nifedipine